We propose to document the occurrence of multiple sclerosis (MS) and Parkinson's disease (PD) among male and female participants of three large ongoing prospective studies and to examine prospectively the association between several dietary and non-dietary risk factors and the incidence of these diseases. The studies are the Nurses' Health Study I (121,000 women), Nurses' Health Study II (116,000 women), and the Health Professionals Follow-up Study (52,000 men). Diet has been assessed repeatedly by a semiquantitative food frequency questinnaire developed and refined by our group over the last 15 years; detailed studies in subsamples of participants demonstrate that this questionnaire performs well, and that the study populations have substantial various in dietary intakes. Several follow-up cycles have been completed, with responses over 90 percent. Numerous non-dietary variables of potential interest as risk factors for MS and Parkinson's disease or as potential confounders of the associations between diet and these diseases have also already been collected at baseline and during the follow-up. We will evaluate the association between history of childhood infections or exposure to dogs potentially infected with the cannine distemper virus and risk of multiple sclerosis by conducting a nested case-control study. In addition, we will examine the association between selected mutations of CYP-2D6-one of the cytochrome P450 enzymes-and risk of PD, and the potential interaction between CPY-2D6 mutations and cigarette smoking as risk factors for PD. The CYP-2D6 genotype will be determined using blood samples that have already been collected, or buccal smears that will be obtained as part of this grant from cases of PD for whom on blood samples are available. The proposed investigation is a highly cost-effective way for studying diet and MS and PD because it draws on a large amount of information already collected and processed, and because the cost of mailing and processing of the foollow-up questionnaires is provided by other sources (CA 55075, CA 40356, CA 50385). Reported cases of MS and PD will be confirmed by supplementary questionnaires sent to the patients and their physicians. Fatal events are identified by next-of-kin, postal service, or the National Death Index and confirmed by hospital records and other additional information. By the end of the follow-up, we project a total of 461 confirmed cases of MS and 380 confirmed cases of PD. We will have sufficient poser to evaluate a series of specific hypotheses with substantial public health implications.